Chromosomal rearrangements, deletions, and other aberrations have long been associated with genetic diseases. Structural abnormalities in chromosomes often arise from errors in homologous recombination. Aneuploidy also referred to as numerical abnormality, in which the chromosome content of a cell is abnormal, may occur as a result of nondisjunction of chromosomes during meiosis. Trisomies, in which three copies of a chromosome are present instead of the usual two, are seen in Edwards, Patau and Down syndromes. Structural abnormalities and aneuploidy can occur in gametes and therefore will be present in all cells of an affected person's body, or they can occur during mitosis and give rise to a genetic mosaic individual who has some normal and some abnormal cells.
Genomic instability also leads to complex patterns of chromosomal rearrangements in certain cells, such as cancer cells, for example. Standard cytogenetic assays such as Giemsa (G) banding have identified numerous cancer-specific translocations and chromosomal abnormalities in cancer cells such as the Philadelphia (t9, 22) chromosome. Down syndrome (a trisomy), Jacobsen syndrome (a deletion) and Burkitt's lymphoma (a translocation) have traditionally been studied via karyotype analysis.
Improvements in cytogenetic banding and visualization such as M banding and spectral karyotyping (SKY) have enabled detailed analyses of inversions and translocations, as well as the identification of unbalanced gain or loss of chromosomal material in cancers of interest. Fluorescence in situ hybridization (FISH) further allows for the detection of the presence or absence of specific DNA sequences on chromosomes by using fluorescent probes that bind to only those parts of the chromosome with which they show a high degree of complementarity.
There is a large unmet need to develop technical methods that detect chromosomal abnormalities.